Amanda A. Fox, M.D., and her co-investigators from the Department of Anesthesiology, Perioperative and Pain Medicine, Brigham and Women’s Hospital and the Division of Cardiovascular Anesthesiology at the Texas Heart Institute, identified variants in two sets of genes that, when added into a clinical model for predicting heart function, offer significant improvement in the ability to anticipate heart problems after surgery.

“The gene variants we studied have been associated with cardiovascular disease states such as hypertension, stroke and myocardial infarction,” said Dr. Fox. “However, to date, the association between these genes and development of heart failure after cardiac surgery with cardiopulmonary bypass has not been examined.”

Dr. Fox’s research focused on a group of protein hormones called natriuretic peptides, which are secreted by heart muscle cells. These natriuretic peptides help to stabilize the body by controlling such things as the amount of water, sodium, potassium and fats in the bloodstream.

Dr. Fox hypothesized that gene variants in natriuretic peptides could independently predict which patients might have poor heart muscle function after heart surgery. Such knowledge would lead to a better understanding of molecular mechanisms underlying postoperative heart failure.

In a companion editorial to the study, John H. Eisenach, M.D., stated that Dr. Fox’s research could be an important next step in clinical genomics.

“The magnitude of this modern collaborative clinical trial is remarkable,” said Dr. Eisenach, Mayo Clinic, Rochester. “This study has potential implications for the prediction of postoperative morbidity, development of disease prevention strategies and personalized pharmacological interventions that pertain to the natriuretic pathway.”

Dr. Fox said that future research needs to broaden the scope of genetic associations in other cardiac surgical patients. Her study included 697 Caucasian subjects.

“The gene variants we studied differ in frequency between people depending upon ethnic backgrounds, requiring that analysis of these variants be stratified by race,” she said.

Dr. Eisenach sees studies such as the one by Dr. Fox and her group as signaling new directions in clinical genomics, a formative field in anesthesiology research.

“The mind-bending speed of genomic technology and discovery has outpaced genomic education in medical school and anesthesiology residency,” he said. “Eventually, education in genomics will be essential for practitioners to translate genomic discoveries into clinical practice.”

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